Adalimumab Therapy in Pediatric Crohn Disease: A 2-Year Follow-Up Comparing Top-Down and Step-Up Strategies

Objectives:European Crohn's Colitis Organization (ECCO) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guidelines recommend the early use of anti-tumor necrosis factor (TNF) biologicals in pediatric Crohn disease (CD) patients with positive predictors for poor outcome. The objective of the present study was to compare early Top-Down use of adalimumab (ADA) immunomodulator/biologics-naive patients to conventional Step-Up management. Methods:One hundred and twenty consecutive patients with a confirmed diagnosis of CD and treated with ADA between 2008 and 2019 were included and allocated to the ADA-Top Down (n = 59) or ADA-Step Up group (n = 61). The primary endpoint was prolonged steroid-/enteral nutrition-free clinical remission at 24 months, defined by a weighted Pediatric Crohn's Disease Activity Index (wPCDAI) < 12.5. Clinical and biological data were collected at 12 and 24 months. Results:At start of ADA, disease activity was comparable between the ADA-Top Down group and the ADA-Step Up group (wPCDAI = 31 +/- 16 vs 31.3 +/- 15.2, respectively, P = 0.84). At 24 months, the remission rate was significantly higher in the ADA-Top Down group (73% vs 51%, P < 0.01). After propensity score, the Top-Down strategy is still more effective than the Step-Up strategy in maintaining remission at 24 months [hazard ratio (HR) = 0.36, 95% CI (0.15-0.87), P = 0.02]. Patients in the ADA-Top Down group were mainly on monotherapy compared to patients in the ADA-Step Up group (53/55 vs 28/55 respectively, P < 0.001). Serum levels of ADA were higher in the ADA-Top Down group than in the ADA-Step Up group (12.8 +/- 4.3 vs 10.4 +/- 3.9 mu g/mL, respectively, P < 0.01). There were no serious adverse events. Conclusions:Early use of ADA appears to be more effective in maintaining relapse-free remission at 2 years, while using it as monotherapy. These findings further favor the recommendation of early anti-TNF use in high-risk CD patients.

Automated summary

The study found that early use of Adalimumab (ADA) in pediatric Crohn's disease patients can effectively maintain remission, especially when used as monotherapy.